Single-cell RNA sequencing integrated with bulk RNA sequencing analysis identifies a tumor immune microenvironment-related lncRNA signature in lung adenocarcinoma.

BACKGROUND: Recently, long non-coding RNAs (lncRNAs) have been demonstrated as essential roles in tumor immune microenvironments (TIME). Nevertheless, researches on the clinical significance of TIME-related lncRNAs are limited in lung adenocarcinoma (LUAD). METHODS: Single-cell RNA sequencing and bulk RNA sequencing data are integrated to identify TIME-related lncRNAs. A total of 1368 LUAD patients are enrolled from 6 independent datasets. An integrative machine learning framework is introduced to develop a TIME-related lncRNA signature (TRLS). RESULTS: This study identified TIME-related lncRNAs from integrated analysis of single­cell and bulk RNA sequencing data. According to these lncRNAs, a TIME-related lncRNA signature was developed and validated from an integrative procedure in six independent cohorts. TRLS exhibited a robust and reliable performance in predicting overall survival. Superior prediction performance barged TRLS to the forefront from comparison with general clinical features, molecular characters, and published signatures. Moreover, patients with low TRLS displayed abundant immune cell infiltration and active lipid metabolism, while patients with high TRLS harbored significant genomic alterations, high PD-L1 expression, and elevated DNA damage repair (DDR) relevance. Notably, subclass mapping analysis of nine immunotherapeutic cohorts demonstrated that patients with high TRLS were more sensitive to immunotherapy. CONCLUSIONS: This study developed a promising tool based on TIME-related lncRNAs, which might contribute to tailored treatment and prognosis management of LUAD patients.

An Enzymatically Activated and Catalytic Hairpin Assembly-Driven Intelligent AND-Gated DNA Network for Tumor Molecular Imaging.

Due to the potential off-tumor signal leakage and limited biomarker content, there is an urgent need for stimulus-responsive and amplification-based tumor molecular imaging strategies. Therefore, two tetrahedral framework DNA (tFNA-Hs), tFNA-H1AP, and tFNA-H2, were rationally engineered to form a polymeric tFNA network, termed an intelligent DNA network, in an AND-gated manner. The intelligent DNA network was designed for tumor-specific molecular imaging by leveraging the elevated expression of apurinic/apyrimidinic endonuclease 1 (APE1) in tumor cytoplasm instead of normal cells and the high expression of miRNA-21 in tumor cytoplasm. The activation of tFNA-H1AP can be achieved through specific recognition and cleavage by APE1, targeting the apurinic/apyrimidinic site (AP site) modified within the stem region of hairpin 1 (H1AP). Subsequently, miRNA-21 facilitates the hybridization of activated H1AP on tFNA-H1AP with hairpin 2 (H2) on tFNA-H2, triggering a catalytic hairpin assembly (CHA) reaction that opens the H1AP at the vertices of tFNA-H1AP to bind with H2 at the vertices of tFNA-H2 and generate fluorescence signals. Upon completion of hybridization, miRNA-21 is released, initiating the subsequent cycle of the CHA reaction. The AND-gated intelligent DNA network can achieve specific tumor molecular imaging in vivo and also enables risk stratification of neuroblastoma patients.

Method to overlay an interference field over a grating using only the grating's profile symmetry.

We theoretically present and experimentally validate a method to overlay the interference field (for making straight-line holographic gratings) with a real grating and a derived method to measure the lateral shift between two real gratings. The methods rely only on the real gratings' profile symmetry, and they are robust against variations of the real gratings' profile parameters and functional form.

Predictive value of CT and 18F-FDG PET/CT features on spread through air space in lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma, a leading cause of cancer-related mortality, demands precise prognostic indicators for effective management. The presence of spread through air space (STAS) indicates adverse tumor behavior. However, comparative differences between 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography(PET)/computed tomography(CT) and CT in predicting STAS in lung adenocarcinoma remain inadequately explored. This retrospective study analyzes preoperative CT and 18F-FDG PET/CT features to predict STAS, aiming to identify key predictive factors and enhance clinical decision-making. METHODS: Between February 2022 and April 2023, 100 patients (108 lesions) who underwent surgery for clinical lung adenocarcinoma were enrolled. All these patients underwent 18F-FDG PET/CT, thin-section chest CT scan, and pathological biopsy. Univariate and multivariate logistic regression was used to analyze CT and 18F-FDG PET/CT image characteristics. Receiver operating characteristic curve analysis was performed to identify a cut-off value. RESULTS: Sixty lesions were positive for STAS, and 48 lesions were negative for STAS. The STAS-positive was frequently observed in acinar predominant. However, STAS-negative was frequently observed in minimally invasive adenocarcinoma. Univariable analysis results revealed that CT features (including nodule type, maximum tumor diameter, maximum solid component diameter, consolidation tumor ratio, pleural indentation, lobulation, spiculation) and all 18F-FDG PET/CT characteristics were statistically significant difference in STAS-positive and STAS-negative lesions. And multivariate logistic regression results showed that the maximum tumor diameter and SUVmax were the independent influencing factors of CT and 18F-FDG PET/CT in STAS, respectively. The area under the curve of maximum tumor diameter and SUVmax was 0.68 vs. 0.82. The cut-off value for maximum tumor diameter and SUVmax was 2.35 vs. 5.05 with a sensitivity of 50.0% vs. 68.3% and specificity of 81.2% vs. 87.5%, which showed that SUVmax was superior to the maximum tumor diameter. CONCLUSION: The radiological features of SUVmax is the best model for predicting STAS in lung adenocarcinoma. These radiological features could predict STAS with excellent specificity but inferior sensitivity.

Abnormal temporal variability of thalamo-cortical circuit in patients with moderate-to-severe obstructive sleep apnea.

This study investigated the abnormal dynamic functional connectivity (dFC) variability of the thalamo-cortical circuit in patients with obstructive sleep apnea (OSA) and explored the relationship between these changes and the clinical characteristics of patients with OSA. A total of 91 newly diagnosed patients with moderate-to-severe OSA and 84 education-matched healthy controls (HCs) were included. All participants underwent neuropsychological testing and a functional magnetic resonance imaging scan. We explored the thalamo-cortical dFC changes by dividing the thalamus into 16 subregions and combining them using a sliding-window approach. Correlation analysis assessed the relationship between dFC variability and clinical features, and the support vector machine method was used for classification. The OSA group exhibited increased dFC variability between the thalamic subregions and extensive cortical areas, compared with the HCs group. Decreased dFC variability was observed in some frontal-occipital-temporal cortical regions. These dFC changes positively correlated with daytime sleepiness, disease severity, and cognitive scores. Altered dFC variability contributed to the discrimination between patients with OSA and HCs, with a classification accuracy of 77.8%. Our findings show thalamo-cortical overactivation and disconnection in patients with OSA, disrupting information flow within the brain networks. These results enhance understanding of the temporal variability of thalamo-cortical circuits in patients with OSA.

Altered functional connectivity of cerebellar subregions in male patients with obstructive sleep apnea: A resting-state fMRI study.

PURPOSE: Previous studies have demonstrated impaired cerebellar function in patients with obstructive sleep apnea (OSA), which is associated with impaired cognition. However, the effects of OSA on resting-state functional connectivity (FC) in the cerebellum has not been determined. The purpose of this study was to investigate resting-state FC of the cerebellar subregions and its relevance to clinical symptoms in patients with OSA. METHODS: Sixty-eight patients with OSA and seventy-two healthy controls (HCs) were included in the study. Eight subregions of the cerebellum were selected as regions of interest, and the FC values were calculated for each subregion with other voxels. A correlation analysis was performed to examine the relationship between clinical and cognitive data. RESULTS: Patients with OSA showed higher FC in specific regions, including the right lobule VI with the right posterior middle temporal gyrus and right angular gyrus, the right Crus I with the bilateral precuneus/left superior parietal lobule, and the right Crus II with the precuneus/right posterior cingulate cortex. Furthermore, the oxygen depletion index was negatively correlated with aberrant FC between the right Crus II and the bilateral precuneus / right posterior cingulate cortex in OSA patients (p = 0.004). CONCLUSION: The cerebellum is functionally lateralized and closely linked to the posterior default mode network. Higher FC is related to cognition, emotion, language, and sleep in OSA. Abnormal FC may offer new neuroimaging evidence and insights for a deeper comprehension of OSA-related alterations.

Internal mechanism of perfect-reflector-backed dielectric gratings to achieve 100% diffraction efficiency.

The work started 20 years ago [Appl. Opt.42, 6255 (2003)APOPAI0003-693510.1364/AO.42.006255] investigating the physical mechanism of multilayer dielectric reflection gratings to achieve 100% diffraction efficiency is completed to offer much deeper insight than before. How different scattering matrix elements of the top periodic surface corrugation contribute to the -1st-order efficiency of such a compound grating is unveiled analytically using a minimum set of real parameters. The two diffraction amplitudes transmitted through the top corrugation play a dominant role in enabling 100% diffraction efficiency. Simple necessary and sufficient conditions for 100% efficiency are derived. Moreover, the role of the reflection phase of the perfect reflector, including the contribution of the optical path between the top corrugation and the reflector, is emphasized.

Comparison of diffusion ranges at different local anesthetic volumes during superior laryngeal nerve block.

OBJECTIVES: Ultrasound-guided superior laryngeal nerve (SLN) block is a practical and painless approach to avoid the hemodynamic stress response during endotracheal intubation and relieve sore throat after laryngeal surgery. The main purpose of this study was to establish an optimal dosage of local anesthetic when performing SLN block to help anesthetists balance analgesia and side effects. METHODS: Twenty fresh larynx specimens were obtained immediately after resection and then injected with 2-, 3-, 4-, or 5- mL of a lidocaine-blue dye mixture at bilateral SLN puncture sites. Superficial areas of deposited blue dye were measured. Dye leakage and surrounding dyed tissue were recorded. Another 40 patients were included in the ultrasound investigation. Distances between the internal branch of the SLN (iSLN) and adjacent structures were calculated. RESULTS: The dye spread area was greater with the administration of larger doses, especially to the visceral space. A 2- or 3-mL injection of local anesthetic was sufficient to infiltrate the SLN gap. A higher incidence of dye leaking out of the thyrohyoid membrane and anterior epiglottis space was observed; furthermore, there was substantially more dyed hyoid/thyroid cartilage with 4 and 5 mL of injected dye mixture than 2 mL. There was no significant difference between the specimen and ultrasound measurements of for length of iSLN-adjacent structures. CONCLUSIONS: In the Chinese population, 2- or 3- mL of local anesthetic is a safe dose during SLN block. A larger volume could overflow from the cavity to cause complications. The thyrohyoid membrane combined with the superior laryngeal artery is a reliable target for positioning the iSLN during ultrasound-guided regional anesthesia.

[Specific changes in gut microbiota and short-chain fatty acid levels in infants with cow's milk protein allergy]. / ç‰›å¥¶è›‹ç™½è¿‡æ•å©´å„¿è‚ é“èŒç¾¤ç‰¹å¼‚æ€§å˜åŒ–åŠçŸ­é“¾è„‚è‚ªé ¸æ°´å¹³åˆ†æž.

OBJECTIVES: To explore the changes in gut microbiota and levels of short-chain fatty acids (SCFA) in infants with cow's milk protein allergy (CMPA), and to clarify their role in CMPA. METHODS: A total of 25 infants diagnosed with CMPA at Children's Hospital Affiliated to Zhengzhou University from August 2019 to August 2020 were enrolled as the CMPA group, and 25 healthy infants were selected as the control group. Fecal samples (200 mg) were collected from both groups and subjected to 16S rDNA high-throughput sequencing technology and liquid chromatography-mass spectrometry to analyze the changes in gut microbial composition and metabolites. Microbial diversity was analyzed in conjunction with metabolites. RESULTS: Compared to the control group, the CMPA group showed altered gut microbial structure and significantly increased α-diversity (P<0.001). The abundance of Firmicutes, Clostridiales and Bacteroidetes was significantly decreased, while the abundance of Sphingomonadaceae, Clostridiaceae_1 and Mycoplasmataceae was significantly increased in the CMPA group compared to the control group (P<0.001). Metabolomic analysis revealed reduced levels of acetic acid, butyric acid, and isovaleric acid in the CMPA group compared to the control group, and the levels of the metabolites were positively correlated with the abundance of SCFA-producing bacteria such as Faecalibacterium and Roseburia (P<0.05). CONCLUSIONS: CMPA infants have alterations in gut microbial structure, increased microbial diversity, and decreased levels of SCFA, which may contribute to increased intestinal inflammation.

Cerebrospinal fluid circulating tumor DNA contributes to the detection and characterization of leptomeningeal metastasis in non-small cell lung cancer.

PURPOSE: Cerebrospinal fluid (CSF) has revealed the unique genetic characteristics of leptomeningeal metastasis (LM) from non-small cell lung cancer (NSCLC). However, the research in this area is still very limited. METHODS: Patients with LM from NSCLC (n = 80) were retrospectively analyzed. Circulating tumor DNA (ctDNA) in CSF was tested by next-generation sequencing (NGS), with paired extracranial tissue or plasma samples included for comparison. An independent non-LM cohort (n = 100) was also analyzed for comparative purposes. Clinical outcomes were compared with Kaplan-Meier log-rank test and Cox proportional hazards methodologies. RESULTS: An overwhelming 93.8% of patients carried druggable mutations in NSCLC LM, with EGFR (78.8%) being the most prevalent. Notably, 4 patients who tested negative for driver genes in extracranial samples surprisingly showed EGFR mutations in their CSF and subsequently benefited from targeted therapy. There was a clear difference in genetic profiles between CSF and extracranial samples, with CSF showing more driver gene detections, increased Copy Number Variations (CNVs), and varied resistance mechanisms among individuals. Abnormalities in cell-cycle regulatory molecules were highly enriched in LM (50.9% vs 31.0%, p = 0.017), and CDKN2A/2B deletions were identified as an independent poor prognostic factor for LM patients, with a significant reduction in median OS (p = 0.013), supported by multivariate analysis (HR 2.63, 95% CI 1.32-5.26, p = 0.006). CONCLUSIONS: CSF-based ctDNA analysis is crucial for detecting and characterizing genetic alterations in NSCLC LM. The distinct genetic profiles in CSF and extracranial tissues emphasize the need for personalized treatment approaches.

Effects of Various Flavors of Baijiu on the Microbial Communities, Metabolic Pathways, and Flavor Structures of Dongbei Suancai.

This study aimed to assess the effects of Chinese Baijiu with different flavors as supplementary material on microbial communities and flavor formation during inoculated fermentation of Chinese Dongbei Suancai. The results showed that the addition of Fen flavor Baijiu significantly increased the relative abundance of Candida, Luzhou flavor Baijiu increased the relative abundance of Pedobacter and Hannaella, while Maotai flavor Baijiu increased the Chryseobacterium and Kazachstania. A total of 226 volatile metabolites were detected in Suancai fermented when adding different flavors of Baijiu. Furthermore, the significantly upregulated metabolites (p < 0.01) of Suancai after adding Baijiu increased by 328.57%, whereas the significantly downregulated metabolites decreased by 74.60%. Simultaneously, the addition of Baijiu promoted the synthesis and decomposition of amino acids and short-chain fatty acids in the early and middle stages of fermentation. Further, Maotai flavor Baijiu improved the diversification of metabolic pathways in the late stage of Suancai fermentation. The E-nose response showed that sulfur-organic, broad-alcohol, sulfur-chlor was the principal differential flavor in Suancai caused by adding Baijiu with different flavors. Simultaneously, Fen flavor Baijiu and Luzhou flavor Baijiu accelerated the formation of the Suancai flavor. These results indicated that Baijiu with different flavors had significant effects on the flavor formation of inoculated fermented Suancai.

Critical review on the research of chemical structure, bioactivities, and mechanism of actions of Dendrobium officinale polysaccharide.

Dendrobium officinale (Tie-Pi-Shi-Hu) is a precious traditional Chinese medicine (TCM). The principal active components are polysaccharides (DOP), which have a high potency in therapeutic applications. However, limitations in structure analysis and underlying mechanism investigation impede its further research. This review systemically and critically summarises current understanding in both areas, and points out the influence of starch impurities and the role of gut microbiota in DOP research. As challenges faced in studying natural polysaccharide investigations are common, this review contributes to a broader understanding of polysaccharides beyond DOP.

A multiplex one-step fluorescence quantitative differential diagnosis method for severe hand, foot and mouth disease caused by coxsackievirus A16.

Hand foot and mouth disease (HFMD) is a common childhood infectious disease which is caused by human enterovirus. The objective of this study was to develop a rapid, sensitive, and accurate method for detecting severe HFMD caused by coxsackievirus A16 (CV-A16). A closed-tube sensitive multiplex one-step reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) was applied to detect CV-A16 in the early stage of severe HFMD. This assay targeted the CV-A16 structure protein VP1 to distinguish CV-A16 from other coxsackieviruses The 5'UTR region of enteric viruses was used for detecting the enterovirus and ribonuclease P (RNaseP) was adopted as the internal reference gene. The multiplex MGB probe assay system was used to detect PCR amplicons with different fluorescence reporters in the same system. The limit of detection (LOD) of the RT-qPCR assay for the CV-A16 VP1 gene was 125.893 copies/µl, for the 5' UTR was 50.1187 copies/µl and for the RNaseP gene was 158.49 copies/µl. Furthermore, specificity analysis showed that the multiplex RT-PCR had no cross-reactivity with the influenza virus, herpangina virus and SARS-COV-2. In correlation analysis, the sensitivity of the multiplex RT-qPCR assay for CV-A16 detection was 100 % (288/288) and the specificity of the multiplex RT-qPCR assay was 99.94 % (3395/3397). The overall agreement between the multiplex RT-qPCR and the results of clinical diagnosis was 99.95 % (3683/3685) and kappa value was 0.996 (p<0.001). The entire procedure, from specimen processing to result reporting, could be completed within 1.5 hours. The one-step multiplex RT-qPCR assay for detecting CV-A16 developed in this study is a good laboratory diagnostic tool for rapid and reliable distinguished detection of CV-A16, especially for severe HFMD patients at an early stage in the disease with low virus load of CV-A16.

A hybrid ResNet-ViT approach to bridge the global and local features for myocardial infarction detection.

Myocardial infarction (MI) remains a significant contributor to global mortality and morbidity, necessitating accurate and timely diagnosis. Current diagnostic methods encounter challenges in capturing intricate patterns, urging the need for advanced automated approaches to enhance MI detection. In this study, we strive to advance MI detection by proposing a hybrid approach that combines the strengths of ResNet and Vision Transformer (ViT) models, leveraging global and local features for improved accuracy. We introduce a slim-model ViT design with multibranch networks and channel attention mechanisms to enhance patch embedding extraction, addressing ViT's limitations. By training data through both ResNet and modified ViT models, we incorporate a dual-pathway feature extraction strategy. The fusion of global and local features addresses the challenge of robust feature vector creation. Our approach showcases enhanced learning capabilities through modified ViT architecture and ResNet architecture. The dual-pathway training enriches feature extraction, culminating in a comprehensive feature vector. Preliminary results demonstrate significant potential for accurate detection of MI. Our study introduces a hybrid ResNet-ViT model for advanced MI detection, highlighting the synergy between global and local feature extraction. This approach holds promise for elevating MI classification accuracy, with implications for improved patient care. Further validation and clinical applicability exploration are warranted.

Anatomical Variations of the Ascending Pharyngeal Artery: Implications for Endoscopic Surgery in the Parapharyngeal Space.

Objectives: The ascending pharyngeal artery (APA) travels with the parapharyngeal internal carotid artery (pICA) in the parapharyngeal space (PPS). This study aimed to investigate the anatomical variations of the APA, and to explore their implications for endoscopic surgery in the PPS. Methods: Dissection of the APA in the PPS was performed on 10 cadaveric specimens (20 sides). The relationship between APA and PPS tumors was retrospectively reviewed in 20 patients, attempting to ascertain the APA during the resection of 10 pre-styloid and 10 retro-styloid PPS tumors. Results: During the cadaveric dissections, the APA was identified at the medial, posteromedial, or bilateral aspects of the pICA in 12 (60%) and 4 (20%) sides, respectively. In the remaining 4 sides (20%), the APA branched into several subcategory arteries lying at the medial and lateral aspects of the pICA. Branches of the APA were observed in 13/20 sides (65%). Two branches were found in 9/13 sides and 3 branches in 4/13, respectively. The APA was only identifiable in 1/10 (10%) of pre-styloid tumors, a patient with basal cell adenoma. In contrast, the APA was encountered surrounding the pICA in 8/10 (80%) of patients with retro-styloid tumors, all of which were schwannomas. No inadvertent injury of the APA or the pICA occurred in this cohort. Conclusions: With identification of the ascending pharyngeal artery on preoperative magnetic resonance imaging, it may serve as an additional landmark during the endoscopic extirpation of tumors arising in the PPS.

Relationship between biofilm formation and antibiotic resistance of Klebsiella pneumoniae and updates on antibiofilm therapeutic strategies.

Klebsiella pneumoniae is a Gram-negative bacterium within the Enterobacteriaceae family that can cause multiple systemic infections, such as respiratory, blood, liver abscesses and urinary systems. Antibiotic resistance is a global health threat and K. pneumoniae warrants special attention due to its resistance to most modern day antibiotics. Biofilm formation is a critical obstruction that enhances the antibiotic resistance of K. pneumoniae. However, knowledge on the molecular mechanisms of biofilm formation and its relation with antibiotic resistance in K. pneumoniae is limited. Understanding the molecular mechanisms of biofilm formation and its correlation with antibiotic resistance is crucial for providing insight for the design of new drugs to control and treat biofilm-related infections. In this review, we summarize recent advances in genes contributing to the biofilm formation of K. pneumoniae, new progress on the relationship between biofilm formation and antibiotic resistance, and new therapeutic strategies targeting biofilms. Finally, we discuss future research directions that target biofilm formation and antibiotic resistance of this priority pathogen.

An APE1 gated signal amplified biosensor driven by catalytic hairpin assembly for the specific imaging of microRNA in situ.

In situ imaging of microRNA (miRNA) content and distribution is valuable for monitoring tumor progression. However, tumor specific in situ imaging remains a challenge due to low miRNA abundance, lack of biological compatibility, and poor specificity. In this study, we designed a DNA tetrahedral framework complex with hairpins (DTF-HPAP) consisting of an apurinic/apyrimidinic site (AP site) that could be specifically recognized and cleaved by apurinic/apyrimidinic endonuclease 1 (APE1). Efficient and specific in situ imaging of miR-21 in tumors was thus achieved through catalytic hairpin assembly (CHA) reaction. In this study, DTF-HPAP was successfully constructed to trigger the cumulative amplification of fluorescence signal in situ. The specificity, sensitivity and serum stability of DTF-HPAP were verified in vitro, and DTF-HPAP could be easily taken up by cells, acting as a biosensor to detect tumors in mice. Furthermore, we verified the ability of DTF-HPAP to specifically image miR-21 in tumors, and demonstrated its capability for tumor-specific imaging in clinical samples.

Microstructural Changes in the Cerebral White Matter After 12 Months of CPAP Treatment for Moderate to Severe Obstructive Sleep Apnoea: A TBSS Study.

Introduction: Continuous positive airway pressure (CPAP) therapy improves clinical symptoms in patients with obstructive sleep apnea (OSA); however, the mechanism of this clinical improvement and how it may be associated with the restoration of white matter (WM) structures in the brain is unclear. Therefore, this study investigated the relationship between the structural recovery of brain WM and improvements in cognitive function and emotion after long-term (12 months) CPAP treatment in patients with OSA. Methods: We collected data from 17 patients with OSA before and 12 months after CPAP treatment, including sleep monitoring, clinical assessment, and diffusion tensor imaging (DTI) magnetic resonance imaging. Results: We observed a partial reversible recovery of brain WM (mean and radial diffusion coefficients) after treatment. This recovery involved the commissural fibers (cingulum, body of corpus callosum), projection fibers (retrolenticular part of the internal capsule, posterior thalamic radiation, posterior limb of the internal capsule, superior corona radiata, posterior corona radiata), association fibers (external capsule, superior longitudinal fasciculus, inferior longitudinal fasciculus), and other regions. In addition, the improvements in WM fibers in one part of the brain significantly were correlated with the Hamilton Anxiety Scale and Hamilton Depression Scale scores. Discussion: Our results suggest that reversible recovery of reduced brain WM integrity due to OSA may require longer CPAP treatment. Moreover, changes in the integrity of the commissural fibers were associated with emotion regulation. These restored WM areas may explain the cognitive and mood improvements observed after OSA treatment.

Functionalizing tetrahedral framework nucleic acids-based nanostructures for tumor in situ imaging and treatment.

Timely in situ imaging and effective treatment are efficient strategies in improving the therapeutic effect and survival rate of tumor patients. In recent years, there has been rapid progress in the development of DNA nanomaterials for tumor in situ imaging and treatment, due to their unsurpassed structural stability, excellent material editability, excellent biocompatibility and individual endocytic pathway. Tetrahedral framework nucleic acids (tFNAs), are a typical example of DNA nanostructures demonstrating superior stability, biocompatibility, cell-entry performance, and flexible drug-loading ability. tFNAs have been shown to be effective in achieving timely tumor in situ imaging and precise treatment. Therefore, the progress in the fabrication, characterization, modification and cellular internalization pathway of tFNAs-based functional systems and their potential in tumor in situ imaging and treatment applications were systematically reviewed in this article. In addition, challenges and future prospects of tFNAs in tumor in situ imaging and treatment as well as potential clinical applications were discussed.

Breakthrough of solid tumor treatment: CAR-NK immunotherapy.

As the latest and most anticipated method of tumor immunotherapy, CAR-NK therapy has received increasing attention in recent years, and its safety and high efficiency have irreplaceable advantages over CAR-T. Current research focuses on the application of CAR-NK in hematological tumors, while there are fewer studies on solid tumor. This article reviews the process of constructing CAR-NK, the effects of hypoxia and metabolic factors, NK cell surface receptors, cytokines, and exosomes on the efficacy of CAR-NK in solid tumor, and the role of CAR-NK in various solid tumor. The mechanism of action and the research status of the potential of CAR-NK in the treatment of solid tumor in clinical practice, and put forward the advantages, limitations and future problems of CAR-NK in the treatment of solid tumor.